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Autosomal recessive congenital ichthyosis caused by CERS3 mutations is extremely rare in clinical practice. We recently identified a family of autosomal recessive congenital ichthyosis and performed multigene exome sequencing for hereditary skin diseases to identify causative genes. Mutation analysis revealed compound heterozygous mutations of c.746A>G(from the mother) and exon12 deletion(from the father)in CERS3 were detected in the proband, which were verified by Sanger sequencing and co-segregated with the ichthyosis phenotype in the proband and her parents. These mutations were both reported for the first time. For the treatment, the proband received an oral acitretin capsules of 20 mg once daily. After 3-month follow up, the patient's lesion improved significantly.
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Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.
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Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.
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Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery, which has merits of biocompatibility, biodegradability and mild gelation conditions. However, its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity. Moreover, for the intracellularly acted proteins, cell membrane as a primary barrier hinders the transmembrane delivery of proteins. The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes. We herein develop a protease-manipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins. The embedded polymeric nanogels (CytoC/aNGs) preserve activity of cytochrome
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@#Lymphatic metastasis is one of the main routes of tumor metastasis. The limitation of traditional medicine in the treatment of lymphatic tumor metastasis lies in the low concentration of the drug in lymphatic metastases resulting in poor efficacy. Nanocarrier-based drug delivery system plays an important role in enhancing drug targeting, improving drug bioavailability, and reducing side effects. This review introduces the composition and function of the lymphatic system as well as its role in tumor metastasis, enumerates the present therapeutic means and limitations of anti-tumor lymphatic metastasis, and focuses on the recent advances in the passive, active and antigen-presenting cell-mediated lymphatic targeted drug delivery systems in tumor metastasis are highlighted.
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Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P<0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P<0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P<0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P<0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P<0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality (HR(95%CI):4.739(2.272-9.885), P<0.01), cardiovascular mortality (HR(95%CI):7.258(2.237-23.548), P=0.001) and MACCE (OR(95%CI):4.143(2.031-8.453), P<0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality (HR(95%CI): 6.387(2.533-16.104), P<0.01), cardiovascular mortality (HR(95%CI): 10.848(2.586-45.506), P=0.001) and MACCE (OR(95%CI): 4.081(1.299-12.816), P=0.016), while not for re-hospitalization for HF (OR(95%CI):1.010(0.700-1.457), P=0.957). Conclusions: Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.
Subject(s)
Female , Humans , China , Heart Failure , Mental Status and Dementia Tests , Prognosis , Prospective StudiesABSTRACT
Objective@#To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis.@*Methods@#In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes.@*Results@#Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P<0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P<0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P<0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P<0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P<0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality (HR(95%CI):4.739(2.272-9.885), P<0.01), cardiovascular mortality (HR(95%CI):7.258(2.237-23.548), P=0.001) and MACCE (OR(95%CI):4.143(2.031-8.453), P<0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality (HR(95%CI): 6.387(2.533-16.104), P<0.01), cardiovascular mortality (HR(95%CI): 10.848(2.586-45.506), P=0.001) and MACCE (OR(95%CI): 4.081(1.299-12.816), P=0.016), while not for re-hospitalization for HF (OR(95%CI):1.010(0.700-1.457), P=0.957).@*Conclusions@#Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.
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Pancreatic cancer is a highly-malignant digestive system neoplasm. The anticancer efficacies of the chemotherapeutic drugs for pancreatic cancer treatment, such as gemcitabine, are greatly limited by their poor targetability to tumor and low drug concentration in the tumor tissue. Drug delivery system plays an important role in improvement of therapeutic efficacy and reduction of adverse effects. Enhancement of the tumor targeting capacity of nanomedicine and promotion of the delivery efficiency are the key issues in the research field of pharmaceutics. In this review article, we survey recent progress in targeted drug delivery nanosystems for treatment of pancreatic cancer by targeting cancer cells, pancreatic tumor stroma, pancreatic cancer-associated cells, and pancreatic cancer stem-like cells, which will provide a new insight into clinical treatment of pancreatic cancer.
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Aim To observe the preventive protection of Yingxindan on acute myocardial ischemia induced by sublingual injection of pituitrin ( pit) in rats.Methods Sixty rats were randomly divided into saline group , model group, nifedipine 12.6 mg · kg -1 group, and Yingxindan 25.2, 12.6, 6.3 mg · kg -1 groups.The saline group and model group were given the same vol-ume of water.After administration for 7 d, an acute myocardial ischemia model was induced by sublingual intravenous injection of pit 1 U · kg -1 in the rats 1 h after last administration .The changes of the II electro-cardiogram(ECG) ST segment at different time points , as well as the positive rate of myocardial ischemia and arrhythmia were observed .Meanwhile , the levels of serum creatine kinase ( CK ) , creatine kinase isoenzyme ( CK-MB ) , glycogen phosphorylase isoenzyme BB ( GPBB ) , cardiac troponin I ( cTnI ) and cardiac troponin T ( cTnT ) were observed .Re-sults Yingxindan could suppress the changes of ST segment of electrocardiogram in rats with acute myocar-dial ischemia induced by pit and reduce the positive rate of myocardial ischemia and arrhythmia .The con-tents of myocardial injury markers CK , CK-MB, GPBB, cTnI and cTnT in serum significantly de-creased, and the corresponding relationship existed . The greater the dose of Yingxindan , the smaller the content of myocardial injuried markers in serum .Con-clusion Yingxindan has significant preventive protec-tion effect on acute myocardial ischemia by pit .
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Objective To analyse of 150 cases of type A aortic dissection anatomic parameter and the relationship between anatomic parameter and clinic date and prognosis.Methods We identified 150 cases of type A aortic dissection who were diagnosed clearly.All patients were divided into groups by gender and surgical approaches.General clinic data and radiological data were recorded.Survival rate was evaluated by follow up 3 months after surgery.Results The aortic root diameter of group aortic root replacement was(53.25±13.17)mm,group aortic root sparing was (49.08±6.94)mm,there was significant difference between the two group(P0.05).There were gender differences between type A dissection parameters of descending aorta,the start diameter of male and female's descending aorta were (41.09±8.86)mm and(37.44±5.60)mm,respectively.The descending aorta in parallel to the pulmonary artery diameter were(34.31±0.59)mm and(31.11±0.88)mm,respectively.Descending aorta diameter of the diaphragm were(31.45±6.50)mm and(28.46±5.20)mm,respectively(all P>0.05).Conclusion In patients who suffer from type A aortic dissection,Parameter of aortic root is one of factors which determine surgical approach to aortic root.When treating descending aorta,surgeon should consider the influence of gender.Our study provided data references for selection and design of endovascular stent-graft.
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@#Nano-drug delivery systems(nano-DDSs)play an important role in targeted cancer therapy. Due to the physiological characteristics of the body and the heterogenicity of tumor, intravenous delivery of anticancer agents carried by nano-DDSs from the injection site to their targeted sites is required to overcome multiple physiological and pathological barriers, including blood, tumor tissue, tumor cell and intracellular transportation. This review surveys emerging strategies for the development of novel nano-DDSs that can conquer the physiological and pathological barriers of tumor, which provides a great potential platform for safe and efficient cancer treatment.